Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice
Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice
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DOI：
10.1016/j.jnutbio.2017.08.006
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发表时间：
2017-12-01
影响因子：
5.6
通讯作者：
Saad, Mario J. A.
中科院分区：
文献类型：
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作者：
Bagarolli, Renata A.;Tobar, Natalia;Saad, Mario J. A.
肥胖和2型糖尿病的特点是亚临床炎症过程。肠道菌群组成或调节的变化可能在肥胖相关的炎症过程中发挥重要作用。在目前的研究中，我们评估了益生菌（鼠李糖乳杆菌、嗜酸乳杆菌和两歧双歧杆菌）对高脂肪饮食和对照动物肠道微生物群、渗透性变化、胰岛素敏感性和信号传导的影响。更重要的是，我们研究了这些肠道调节对下丘脑控制食物摄入、胰岛素和瘦素信号的影响。采用高脂饮食（HFD）加益生菌或配对喂养5周。对小鼠粪便DNA样本进行宏基因组分析。抽血测定葡萄糖、胰岛素、脂多糖、细胞因子和GLP-1的水平。采用Western blotting和实时聚合酶链反应分析肝脏、肌肉、回肠和下丘脑组织蛋白。此外，采用组织学和免疫组织化学方法对肝脏和脂肪组织进行分析。HFD诱导了肠道微生物群的巨大改变，伴随着肠道通透性增加、LPS易位和全身低度炎症，导致糖耐量下降和贪食行为。所有这些与肥胖相关的特征都被益生菌诱导的肠道菌群变化所逆转。益生菌还能改善下丘脑胰岛素和瘦素抵抗。我们的数据表明，肠道微生物组是外周和中枢组织炎症和代谢途径的关键调节剂。这些发现揭示了益生菌作为预防和治疗肥胖和胰岛素抵抗患者的重要工具。(C) 2017爱思唯尔公司版权所有。
Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L. acidophilus and Bifidobacterium bifidumi) on gut microbiota, changes in permeability, and insulin sensitivity and signaling in high-fat diet and control animals. More importantly, we investigated the effects of these gut modulations on hypothalamic control of food intake, and insulin and leptin signaling. Swiss mice were submitted to a high-fat diet (HFD) with probiotics or pair-feeding for 5 weeks. Metagenome analyses were performed on DNA samples from mouse feces. Blood was drawn to determine levels of glucose, insulin, LPS, cytokines and GLP-1. Liver, muscle, ileum and hypothalamus tissue proteins were analyzed by Western blotting and real-time polymerase chain reaction. In addition, liver and adipose tissues were analyzed using histology and immunohistochemistry. The HFD induced huge alterations in gut microbiota accompanied by increased intestinal permeability, LPS translocation and systemic low-grade inflammation, resulting in decreased glucose tolerance and hyperphagic behavior. All these obesity-related features were reversed by changes in the gut microbiota profile induced by probiotics. Probiotics also induced an improvement in hypothalamic insulin and leptin resistance. Our data demonstrate that the intestinal microbiome is a key modulator of inflammatory and metabolic pathways in both peripheral and central tissues. These findings shed light on probiotics as an important tool to prevent and treat patients with obesity and insulin resistance. (C) 2017 Elsevier Inc. All rights reserved.